title: Evidence of canonical somatic hypermutation in hairy cell leukemia.
abstract: To compare hairy cell leukemia (HCL) with chronic lymphocytic leukemia (CLL) and normal B cells with respect to their B-cell receptors, somatic hypermutation (SHM) features in HCL were examined in a series of 130 immunoglobulin gene heavy chain rearrangements, including 102 from 100 classic (HCLc) and 28 from 26 variant (HCLv) patients. The frequency of unmutated rearrangements in HCLc was much lower than that in HCLv (17% vs 54%, P < .001) or historically in CLL (17% vs 46%, P < .001), but HCLv and CLL were similar (P = .45). As previously reported for CLL, evidence of canonical SHM was observed in HCLc rearrangements, including: (1) a higher ratio of replacement to silent mutations in the complementarity determining regions than in the framework regions (2.83 vs 1.41, P < .001), (2) higher transition to transversion ratio than would be expected if mutations were random (1.49 vs 0.5, P < .001), and (3) higher than expected concentration of mutations within RGYW hot spots (13.92% vs 3.33%, P < .001). HCLv met these 3 criteria of canonical SHM to a lesser extent. These data suggest that, whereas HCLc cells may recognize antigen-like CLL and normal B cells before malignant transformation, HCLv cells from some patients may originate differently, possibly without undergoing antigen recognition.
authors.affiliation: Laboratories of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Arons
authors.forename: Laura
authors.initials: L
authors.lastname: Roth
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sapolsky
authors.forename: Tara
authors.initials: T
authors.lastname: Suntum
authors.forename: Maryalice
authors.initials: M
authors.lastname: Stetler-Stevenson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kreitman
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D020029:Base Pairing; D022801:Complementarity Determining Regions / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007943:Leukemia, Hairy Cell / Q000235:genetics* / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D022801:Complementarity Determining Regions; D004273:DNA, Neoplasm; D007135:Immunoglobulin Variable Region